Retrospective analysis of the relationship between time to anti-resorptive therapy and incidence of skeletal related events in patients with multiple myeloma.
Authors: Adam F Binder, Kelly Hughes, Abdullateef Abdulkareem, Adam Barsouk, Niketa Raj, Tingting Zhan, Sai Gundepalli, Srinivas S. Devarakonda
Journal: Journal of Clinical Oncology (2023)

8048 Background: Patients with multiple myeloma (MM) often have bone disease at diagnosis and are at risk of developing skeletal related events (SRE) (pathological fractures, spinal cord compression, and/or need for radiotherapy or surgery to bone). It is well established that for patients with lytic bone lesions at diagnosis, the use of anti-resorptive agents lead to a lower incidence of SREs. However, it is common for initiation of anti-resorptive therapy to be delayed. Recent studies have demonstrated that anti-resorptive therapy is underutilized in patients with MM. However, the effect of time to initiation of anti-resorptive agent after diagnosis of MM on SREs has not been well studied. Herein, we conducted a multi-center retrospective analysis to determine if time to anti-resorptive agent has an adverse impact on the risk of SREs. Methods: We performed a retrospective cohort study using our Electronic Health Record system to identify patients with newly diagnosed MM between July 1 st , 2016 and June 30 th , 2019 at two large academic centers. Patients previously treated or patients not treated with anti-resorptive therapy were excluded. The study’s primary endpoint was hazard ratio of developing a SRE based on time to anti-resorptive therapy. The relationship between incidence of SREs and time to anti-resorptive therapy, gender, age, International Staging System (ISS) stage at diagnosis, and prior SRE present at diagnosis was analyzed by using a multivariable Cox proportional hazards model. The cutoff point of anti-resorptive therapy delay was based on the recursive partitioning of univariable Cox model. Results: 759 patients were included in the study (Thomas Jefferson University: n = 232; The Ohio State University: n = 527). Median age at diagnosis is 60.2 years (IQR: 12.4 years). 57% of patients were male. 77.9% and 20.3% of patients identified as white and black respectively. 210 patients (27.7%) were noted to have osteopenia, 45 (5.9%) had osteoporosis, 229 (30.2%) were vitamin D deficient, and 319 (42%) were obese at diagnosis. A skeletal related event was present at diagnosis in 338 (45.1%) of patients. 180 (34%) patients received anti-resorptive agents within 31 days. A delay in initiating anti-resorptive agents of greater than 31 days from diagnosis had an increased risk for SRE with a hazard ratio 1.654 (1.054~2.598; p-value: 0.029). Conclusions: This large multicenter retrospective study demonstrated that time to anti-resorptive therapy MM patients has a significant impact on the risk of SRE. Given many of the challenges in starting anti-resorptive therapy in a timely manner, this study emphasizes the need for inter-professional, multi-disciplinary collaborations to streamline the workflow and start therapy within the first month of diagnosis. Ongoing efforts are underway to develop quality improvement processes to achieve this goal.